Long-lasting behavioral effects of quinpirole exposure on zebrafish

Abstract

The human brain matures into a complex structure, and to reach its complete development, connections must occur along exact paths. If at any stage, the processes are altered, interrupted, or inhibited, the consequences can be permanent. Dopaminergic signaling participates in the control of physiological functions and behavioral processes, and alterations in this signaling pathway are related to the pathogenesis of several neurological disorders. For this reason, the use of pharmacological agents able to interact with the dopaminergic signaling may elucidate the biological bases of such disorders. We investigated the long-lasting behavioral effects on adult zebrafish after quinpirole (a dopamine D2/D3 receptor agonist) exposure during early life stages of development (24 h exposure at 5 days post-fertilization, dpf) to better understand the mechanisms underlying neurological disorders related to the dopaminergic system. Quinpirole exposure at the early life stages of zebrafish led to late behavioral alterations. When evaluated at 120 dpf, zebrafish presented increased anxiety-like behaviors. At the open tank test, fish remained longer at the bottom of the tank, indicating anxiety-like behavior. Furthermore, quinpirole-treated fish exhibited increased absolute turn angle, likely an indication of elevated erratic movements and a sign of increased fear or anxiety. Quinpirole-treated fish also showed altered swimming patterns, characterized by stereotypic swimming. During the open tank test, exposed zebrafish swims from corner to corner in a repetitive manner at the bottom of the tank. Moreover, quinpirole exposure led to memory impairment compared to control fish. However, quinpirole administration had no effects on social and aggressive behavior. These findings demonstrate that dopaminergic signaling altered by quinpirole administration in the early life stages of development led to late alterations in behavioral parameters of adult zebrafish.